Dunns EXTRA stuff Flashcards
supplementary carbohydrate metabolism
What are glycosaminoglycans?
GAGS
- long unbranched polysaccharides
- repeating disaccharide unit of hexosamine or hexose sugar and uronic acid or hexose sugar
- e.g. Heparin
What can the hexosamines or the hexose sugar be in the GAG?
Hexosamine:
N-acetylglucosamine or N-acetylgalactosamine
Hexose Sugar:
Galactose
What can the uronic acid or the hexose sugar be in the GAG?
Uronic Acid:
Glucuronic acid or iduronic acid
Hexose Sugar:
Galactose
When are the disaccharides in GAGS sulfated?
Most cases
- exception is hyaluronic acid
What are glycosamioglycans disorders?
- lysosomal storage disorders
- inherited diseases called MPS diseases
- defects in lysosomal enzymes associated with metabolism/ breakdowns of GAGs leading to an accumulation of GAGs in cells
Name and describe a MPS disease.
Sanfilippo disease - rare - primarily effects heparan sulfate - causes mental deterioration Effects cornea, heart, lungs, brain and mental functions
Where are GAGs prevalent?
In proteoglycans
What is the structure of proteoglycans?
- protein with one of multiple (>100) GAGs covalently attached
- up to 95% of proteoglycan
- trisaccharide links GAGs to the protein
- large molecules
What are trisaccharides in GAGs composed of?
2 galactose residues and a xylose residue
What are the properties of GAGs?
- highly negatively charged
- highly hydrophilic
What can GAGs do in the body?
- concentrate cations such as sodium
- can form porous hydrated gels that are active in the extracellular matrix providing mechanical support, infused with chains
- can form long chains (withstand compression forces and act as lubricants around joints)
- chains are inflexible
What are glycoproteins?
- oligosaccharide chains covalently linked to proteins
Name an example of a glycoprotein.
Erythropoietin (EPO) is a glycoprotein hormone
- controls rbc production (haemopoiesis)
What are glycoproteins usually composed of?
No GAGs
Usually, glucose, galactose manose etc
- not typically sulfated
How does the ratio of glycoproteins compare to that or proteoglycans?
Protein:sugar ratio is higher, more proteins than hexose sugars in glycoproteins than in proteoglycans
How do we acquire fatty acids?
Through diet
Where can we synthesise fatty acids?
Liver and adipose fat
What are the 4 fatty acid synthesis steps?
- condensation of acetyl-ACP and malonyl ACP
- reduction
- dehydration
- reduction to form butyryl-ACP
- further processes add malonyl-acp to synthesise a c16 or c18 fatty acid
What is ACP?
An acyl carrier protein
Draw the diagram of fatty acid synthesis (including enzymes)
-
Which is the rate-limiting step in fatty acid synthesis?
Synthesis of malonyl-CoA
How do you synthesise malonyl-CoA?
Acetyle-CoA + AYP + HCO3- -> Malonyl-CoA + ADP + Pi + H+
using enzyme acetyl-CoA carboxylase
How do you control fatty acid metabolism?
Regulation of acetyl-CoA carboxylase
What happens during the inactive phase of acetyl-CoA carboxylase?
- post translational phosphorylation
- during fasting state, presence of glucagon and adrenaline (along with protein kinases) will phosphorylate the carboxylase
What happens during the active phase of acetyl-CoA carboxylase?
- inactive phosphate has been dephosphorylated
- during fed state, insulin (along with protein kinase) will dephosphorylate the carboxylase
What is the word for an inactive and active protein complex?
inactive - monomeric
active - polymeric
When can the partially active state for carboxylase occur?
- build of citrate from the TCA cycle
- acetyl-coA is no longer needed in TCA and so can be used in synthesis of fatty acids
- carboxylase is phosphorylated but also has a non covalently bound citrate complex
- partial activation
What is fatty acid elongation?
synthesis of longer than C16/C18 fatty acids, derived form diet and synthesis
What is the difference between fatty acid elongation and fatty acid synthesis?
- occurs in the ER
- applies CoA not ACP conjugates
What are the similarities between fatty acid elongation and fatty acid synthesis?
- applies reductase, hydratase enzymes
- applies malonyl CoA as a 2 C donor
- requires NADPH as a reducing agent
- can operate for saturated and unsaturated fatty acids
What is fatty acid desaturation- aerobic desaturation?
- provides mono or polyunsaturated fatty acids from either saturated or unsaturated fatty acids
What are the 3 desaturase enzymes in mammals? Where do they create double bonds
delta 5,6 and 9
- create double bonds at C position 5, 6 and 9
Which enzymes are involved in fatty acid desaturation?
NADH-cytochrome b5 reductase, cytochrome b5 and desaturase
What are the two essential fatty acids for humans?
Linolenic acid and alpha-linolenic acid
What are Linolenic acid and alpha-linolenic acid used for?
- to generate new fatty acids that have double bonds beyond the C9 position
What are essential fatty acids?
Fatty acids required to be delivered through the diet as cannot be synthesised
What is arachidonic acid?
A precursor for major prostaglandins, inc thromboxane A2 (through thromboxane synthases)
Where can arachidonic acid and other major inflammatory and pain mediators be found in the body? Inc examples.
local hormones produced and applied at site of action
thromboxane A2, generated in blood platelets for vasoconstrictions
Prostaglandin E2, generated in the uterus and generates muscle contractions during brith
What are the COX enzymes used for?
- enzymes involved in the synthesis of PGH2 (prostaglandins H2) from Arachidonic acid
Where are COX 1 & COX 2 enzymes found?
COX 1 is widely expressed in many tissues
COX 2 is not observed in healthy tissues
- inflammatory mediator response
What do anti-inflammatory drugs inhibit?
Aspirin & ibuprofen are non specific and inhibit both
- inhibition of COX1 lead to bleeding and gastric inflammation
- inhibition of COX2 target inflammatory action (more specific effects)
What are steroids?
- class of lipids with 4 fused cycloalkane rings and a C17 backbone
- 3 cyclohexane and 1 cyclopentane ring
What are examples of steroids?
- cholesterol
- bile acid
- progesterone
What is cholesterol?
- steroid
- essential metabolite in mammalian systems and a precursor to other important metabolites
Where is cholesterol synthesises?
cytoplasm mainly in the liver, but also: intestine, adrenal glands and reproductive organs
What are the 3 main steps of cholesterol biosynthesis
step 1: acetyl-CoA to mevalonate
step 2: mevalonate to squalene
step 3: squalene to cholesterol (via lanosterol)
How many moles of acetyl-CoA, ATP and NADPH is used up in the synthesis of cholesterol?
18 moles of acetyl-CoA, 36 moles of ATP and 16 moles of NADPH
